September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Identification of uveitis-associated gut bacteria
Author Affiliations & Notes
  • Iris Lee
    Casey Eye Institute, Portland, Oregon, United States
  • Lisa Karstens
    Rheumatology, OHSU, Portland, Oregon, United States
  • Christina Metea
    Casey Eye Institute, Portland, Oregon, United States
  • Cathleen Moscibrocki
    Casey Eye Institute, Portland, Oregon, United States
  • Mark Asquith
    Rheumatology, OHSU, Portland, Oregon, United States
  • Yukiko K Nakamura
    Casey Eye Institute, Portland, Oregon, United States
  • Phoebe Lin
    Casey Eye Institute, Portland, Oregon, United States
  • Footnotes
    Commercial Relationships   Iris Lee, None; Lisa Karstens, None; Christina Metea, None; Cathleen Moscibrocki, None; Mark Asquith, None; Yukiko Nakamura, None; Phoebe Lin, None
  • Footnotes
    Support  Unrestricted Grant from Research to Prevent Blindness, New York, New York; NIH K08EY022948
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 505. doi:
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      Iris Lee, Lisa Karstens, Christina Metea, Cathleen Moscibrocki, Mark Asquith, Yukiko K Nakamura, Phoebe Lin; Identification of uveitis-associated gut bacteria. Invest. Ophthalmol. Vis. Sci. 2016;57(12):505.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The importance of the gut microbiome in experimental autoimmune uveitis (EAU) was recently established, but the specific pathogenic or protective bacterial constituents are still unknown. The objective of this study was to determine gut bacterial constituents that might either be protective against or promote EAU

Methods : B10.RIII mice were treated with oral antibiotics (1 mg/mL each of ampicillin, neomycin sulfate, or metronidazole, or 0.5 mg/mL of vancomycin) one week prior to immunization with interphotoreceptor binding protein peptide 161-180. DNA was extracted from ileal and cecal contents 3 weeks after immunization. 16s rRNA gene sequencing was performed using Illumina Miseq. QIIME was used for alpha diversity analyses, weighted unifrac distances of clustered operational taxonomic units, and relative abundance compared using the Deseq R package. Data was normalized through rarefication.

Results : EAU mice treated with oral metronidazole (mean clinical score 1.2 vs. 2.8 in control) or vancomycin (1.3 vs. 2.3 in control) had attenuated uveitis, whereas, ampicillin and neomycin had either no effect or worsened uveitis. Bacterial composition by 16s sequencing clustered together in metronidazole and vancomycin, and according to clinical score (Figure 1 and 2). Several specific bacterial genera were observed to be significantly decreased in mice treated with vancomycin and metronidazole: Coprococcus, Ruminococcus, Oscillospira, Dehalobacterium (p = 0.02), Anaeroplasma, and Dorea (p = 0.01). The populations of these bacteria were not significantly impacted by treatment with ampicillin or neomycin. Enterobacteriaceae was the only bacteria increased in both metronidazole and vancomycin-treated animals, but was also increased in ampicillin-treated animals. Certain lactobacilli genera were increased in the ileum of metronidazole-treated animals. All p–values were < 0.001 except where specified.

Conclusions : Gut microbial clustering appears to occur according to clinical severity of uveitis. Specific bacteria identified in this study may be associated with either uveitogenesis or protection against uveitis. Once validated, these findings could provide novel targets for the treatment of uveitis.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

Gut microbiota in metronidazole and vancomycin-treated mice cluster together.

Gut microbiota in metronidazole and vancomycin-treated mice cluster together.

 

Microbiota of EAU mice with lower clinical scores cluster together.

Microbiota of EAU mice with lower clinical scores cluster together.

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